Mechanisms regulating cytotrophoblast invasion in normal pregnancy and pre-eclampsia

The placental bed underlies the placenta and includes the decidua basalis and underlying myometrium containing the uterine spiral arteries. For successful human haemochorial placentation, the placental bed spiral arteries must undergo considerable alterations. These physiological modifications are thought to be brought about by the interaction of invasive cytotrophoblast with the spiral artery vessel wall. Failure of spiral artery transformation is thought to play an important role in the sequence of events that gives rise to pre-eclampsia. The mechanisms that control human trophoblast invasion in normal, let alone abnormal pregnancy, are still poorly understood. Much of the information on the early physiological changes within the placental bed comes from studies on intact hysterectomy specimens.(1) Details of such events in late pregnancy and in pregnancies complicated by pre-eclampsia and fetal growth restriction are principally derived from the study of placental bed biopsies taken at Caesarean section. The methods of sampling the placental bed have been reviewed elsewhere.(2) Many investigators have relied on in vitro models of trophoblast invasion. In vitro models can be extremely useful in dissecting out some of these processes but may be open to artefacts. The mechanisms underlying normal and failed trophoblast invasion appear to be complex. In this manuscript the mechanisms that control the invasion of trophoblast into the decidua and myometrium are reviewed. Along with this is a review of the purported mechanisms underlying failed spiral artery transformation. Particular emphasis has been placed on topics that have been best studied.